Project Summary Since its commercial introduction in 1981, pulse oximetry has become a widely adopted standard of care in operating rooms, intensive care units, and hospital wards. The ability to measure arterial oxygen saturation using pulse oximetry is so useful that it is considered the ?5th vital sign?. Despite their ubiquity, pulse oximeters have suffered from two fundamental limitations since their inception: poor signal quality when patients experience vasoconstriction, and erroneous data caused by motion. Although advanced signal processing techniques have been use commercially to address these problems, false alarms that lead to increased staff workload and decreased vigilance (?alarm fatigue?) remain very common. The long-term goal of the proposed research is the development of a next-generation pulse oximeter which addresses the limitations above by performing arterial blood oxygenation measurements in new and fundamentally different manner than the photoplethysmographic methods used today. The proposed method leverages established blood flow measurement techniques based on light scattering to perform measurements, which results in a signal that is often hundreds of times greater than a typical pulse oximeter signal and which is significantly less susceptible to vasoconstriction and motion. This long-term goal will be achieved by pursuing the following three specific aims: (1) integrating a multi-wavelength VCSEL light source into an established clip-on blood flowmeter, (2) validating this multi-wavelength instrument in a rabbit model via comparison to bench top blood gas analysis during an oxygen challenge, and (3) completing a formal framework for relating SpO2 to measured blood flow waveforms using collected empirical data from in conjunction with Monte Carlo simulations. Aim 1 will be accomplished by modifying instrumentation already developed by the PI to measure blood flow with multi-wavelength light sources fabricated through a commercial partner. Aim 2 will be accomplished through close collaboration with the Beckman Laser Institute and their established veterinary team who performs photonics-based small animal studies daily. Aim 3 will be accomplished by utilizing validated light propagation modeling tools to create a robust lookup table based generated from the data collected in Aim 2.